Early detection of disease states in mammals has been the focus of much recent research. For disease detection, the public-health community has historically relied on laboratory tests that can sometimes take days or even weeks to return a result. The increased availability of better and faster diagnostic tests, however, promises the possibility of more automated and earlier disease detection and subsequent intervention. Early detection of disease can lead to introduction of therapy early in the disease process, as well as to improved therapy methods.
Systemic lupus erythematosus (also called SLE, or lupus) is a chronic inflammatory autoimmune disease that can affect any organ or organ system. The presence of auto-antibodies, especially those directed to double-stranded DNA, is characteristic for the disease. Sometimes called the “great imitator” because its widely varied symptoms are often mistaken for other disorders, SLE has the potential to affect the skin, joints, kidneys, lungs, nervous system, and/or other organs of the body. The most common symptoms of SLE include skin rashes and arthritis, often accompanied by fatigue and fever. Although SLE can be a fatal disease, the clinical course typically varies from mild to severe, and involves alternating periods of remission and relapse.
Among the principal determinants of poor prognosis in SLE is a severe and progressive renal involvement known as lupus nephritis (LN), a complication more frequently encountered in children than adults with the disease. LN is a complication of SLE related to the autoimmune process of SLE, where complexes of antinuclear antibodies and complement accumulate in the kidneys and result in an inflammatory response. LN typically manifests as mild proteinuria, hematuria, azotemia, hypertension, or urine sediment consisting of red blood cell casts, waxy casts, and cellular debris, or any combination of these. However, LN can also manifest as a rapidly progressive glomerulonephritis. Almost every patient with LN has proteinuria, with 45% to 65% of these patients developing the nephrotic syndrome. LN occurs in approximately 50% of patients with SLE within 1 year of diagnosis, and 15% to 20% of these patients develop renal disease severe enough to require renal replacement therapy.
Renal involvement (including worsening renal disease activity and/or LN) is one of the main determinants of poor prognosis of SLE, and is more frequently encountered in children (cSLE) than adults with SLE. Typically, increased disease activity in SLE patients typically cannot be determined by a single laboratory value or clinical sign. For example, proteinuria can be a sign of active LN, but also occurs with renal damage of any cause. While laboratory tests such as BUN, serum creatinine, proteinuria, etc. may help in the diagnosis of worsening SLE renal disease activity, currently available renal biomarkers, e.g. measures of the degree of SLE renal disease activity and severity, are too insensitive and non-specific to allow for the early identification and diagnosis of active SLE nephritis. Further, randomized clinical trials in SLE are hindered by the lack of high-quality biomarkers to allow timely therapy to avoid permanent renal damage or to verify the effects of therapies within a short period of time.
Definitive diagnosis of SLE renal disease is currently established on the basis of a combination of clinical, laboratory, and pathologic findings, and often requires a renal biopsy. Three of these validated measures are the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the British Isles Lupus Assessment Group index (BILAG), and the Systemic Lupus Activity Measure (SLAM). They have been accepted for use in assessing both adults and children with SLE. However, the SLEDAI may be preferable overall.
Because there is no uniquely accepted way to determine worsening disease activity in SLE, the quest for a reliable early biomarker of active LN and/or lupus nephritis caused by SLE is an area of intense contemporary research. An improved method for the early detection of active LN in patients with SLE could lead to improvements in therapy, and could significantly increase life expectancy and quality of life.